Low-dose paclitaxel modulates the cross talk between the JNK and Smad signaling in primary biliary fibroblasts.

Abstract

OBJECTIVE:

The objective of this study was to explore the molecular mechanism underlying the occurrence of benign bile duct stricture and the target of low-dose paclitaxel in the prevention of benign bile duct stricture.

METHODS:

Under the stimulation of transforming growth factor beta 1, the expression of collagen type I and connective tissue growth factor were detected on isolated primary fibroblasts. The phosphorylation levels of JNK and Smad2L were detected using Western blot. The effect of low-dose paclitaxel on the transforming growth factor beta 1-induced inhibition of type I collagen and connective tissue growth factor expression and JNK and Smad2L phosphorylation was also observed.

RESULTS:

Transforming growth factor beta 1 induced the secretion of type I collagen and connective tissue growth factor as well as JNK phosphorylation in biliary fibroblasts. The JNK inhibitor or siRNA-Smad2 inhibited the transforming growth factor beta 1-induced secretion of type I collagen and connective tissue growth factor. Low-dose paclitaxel inhibited the expression of type I collagen induced by transforming growth factor beta 1 and may inhibit the secretion of collagen in biliary fibroblasts.

CONCLUSION:

The activation of JNK/Smad2L induced by transforming growth factor beta 1 is involved in the occurrence of benign bile duct stricture that is mediated by the overexpression of type I collagen and connective tissue growth factor, and low-dose paclitaxel may inhibit the phosphorylation of JNK/Smad2L.

• Authors: Jiamei Lu, Liang Yu, Jianhua Shi
• Journal: Revista da Associacao Medica Brasileira (1992) (Rev Assoc Med Bras (1992)) Vol. 68 Issue 2 Pg. 159-164 (Feb 2022) ISSN: 1806-9282 [Electronic] Brazil
• PMID: 35239875 (Publication Type: Journal Article)

Chemical References

• Collagen Type I
• SMAD2 protein, human
• Smad2 Protein
• Collagen
• Paclitaxel

Topics

• Collagen
• Collagen Type I (metabolism, pharmacology)
• Fibroblasts (metabolism)
• Humans
• MAP Kinase Signaling System
• Paclitaxel (pharmacology)
• Smad2 Protein